scholarly journals Markers of remodeling in subcutaneous adipose tissue are strongly associated with overweight and insulin sensitivity in healthy non-obese men

2020 ◽  
Author(s):  
Sissel Åkra ◽  
Tonje A. Aksnes ◽  
Arnljot Flaa ◽  
Heidi B. Eggesbø ◽  
Trine Baur Opstad ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Plasminogen Activator Inhibitor ◽  
Glucose Disposal ◽  
Middle Aged ◽  
Ecm Remodeling ◽  
Glucose Clamp Technique ◽  
Galectin 3 ◽  
Subcutaneous Adipose ◽  
Diabetes And Obesity ◽  
Activator Inhibitor

Abstract Background Alteration in extracellular matrix (ECM) in adipose tissues (AT) has been associated with insulin resistance, diabetes and obesity. Aim To investigate whether selected biomarkers of ECM remodeling in AT associate with the amount and distribution of abdominal AT and with insulin sensitivity and other glucometabolic variables. Materials and Methods Subcutaneous AT and fasting blood samples were collected in 103 middle-aged healthy non-obese men. Gene expression in AT was determined by RT-PCR and distribution of AT by computed tomography, separated into subcutaneous, deep subcutaneous and visceral AT. Circulating levels were determined by ELISA, and insulin sensitivity was measured by glucose clamp technique, assessing glucose disposal rate (GDR). Results Metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 expression in AT correlated significantly to the amount of AT in all compartments (r s =0.41-0.53, all p ≤0.01), and to insulin sensitivity, insulin, C-peptide, waist circumference and body mass index (BMI) (r s =0.25–0.57, all p ≤0.05). When dichotomizing the glucometabolic variables at median levels the expression of MMP-9 was 5.3 fold higher in subjects with insulin sensitivity below median (GDR<6.3mg/kg/min) ( p =0.002) and 3.1 fold higher in subjects with BMI above median level (>23.5kg/m 2 ) ( p =0.013). Galectin-3 did not associate with the amount of AT, but inversely with insulin and c.peptide ((p<0.01m both). Conclusion In our healthy non-obese middle-aged population AT-expressed genes, central in remodeling of ECM, associated strongly with the amount of abdominal AT, overweight and insulin sensitivity, indicating AT-remodeling to be important also in non-obese individuals. The remodeling process seems furthermore to play a central role for glucometabolic disturbances.

Regional Variation in Plasminogen Activator Inhibitor-1 Expression in Adipose Tissue from Obese Individuals

2000 ◽  
Vol 83 (04) ◽  
pp. 545-548 ◽  
Author(s):  
Vanessa Van Harmelen ◽  
Johan Hoffstedt ◽  
Per Lundquist ◽  
Hubert Vidal ◽  
Veronika Stemme ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Visceral Adipose ◽  
Subcutaneous Adipose ◽  
Activator Inhibitor ◽  
Pai 1

SummaryHigh plasma plasminogen activator inhibitor-1 (PAI-1) activity is a frequent finding in obesity and adipose tissue has recently been suggested to be a source of circulating PAI-1 in humans. In the present study, differences in adipose tissue gene expression and protein secretion rate of PAI-1 between subcutaneous and visceral adipose tissue was analysed in specimens obtained from 22 obese individuals. The secretion rate of PAI-1 was two-fold higher in subcutaneous adipose tissue than in visceral adipose tissue (292 ± 50 vs 138 ± 24 ng PAI-1/107 cells, P <0.05). In accordance with the secretion data, subcutaneous adipose tissue contained about three-fold higher levels of PAI-1 mRNA than visceral adipose tissue (2.43 ± 0.37 vs 0.81 ± 0.12 attomole PAI-1 mRNA/µg total RNA, P <0.001). PAI-1 secretion from subcutaneous but not from visceral adipose tissue correlated significantly with cell size (r = 0.43, P <0.05). In summary, subcutaneous adipose tissue secreted greater amounts of PAI-1 and had a higher PAI-1 gene expression than visceral adipose tissue from the same obese individuals. Bearing in mind that subcutaneous adipose tissue is the largest fat depot these finding may be important for the coagulation abnormalities associated with obesity.

scholarly journals Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men

2003 ◽  
Vol 88 (7) ◽  
pp. 3190-3195 ◽  
Author(s):  
Hiroaki Kawano ◽  
Hirofumi Yasue ◽  
Akira Kitagawa ◽  
Nobutaka Hirai ◽  
Toshiaki Yoshida ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Steady State ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Plasminogen Activator Inhibitor ◽  
Age Related ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

The dehydroepiandrosterone (DHEA) concentration decreases with age. There is evidence that DHEA has a protective effect against age-related disorders, including cardiovascular disease. Accordingly, we examined the effect of DHEA supplementation (25 mg/d) on endothelial function, insulin sensitivity, and fibrinolytic activity in 24 men with hypercholesterolemia (mean age, 54 ± 1 yr). All subjects were enrolled in a randomized, double-blind study. Flow-mediated dilation of brachial artery after transient occlusion, which was expressed as the percent change from the baseline value of the diameter, increased significantly with DHEA supplementation [DHEA: baseline, 3.9 ± 0.5%; 4 wk, 6.9 ± 0.7%; 8 wk, 7.9 ± 0.6%; 12 wk, 8.4 ± 0.7% (P &lt; 0.01 vs. baseline for all, by ANOVA); placebo: 4.1 ± 0.6%, 4.5 ± 0.5%, 3.9 ± 0.5%, and 4.4 ± 0.6% (P &lt; 0.01 for all, by ANOVA)]. There was a significant concurrent reduction in the plasma levels of plasminogen activator inhibitor type 1 during DHEA supplementation [DHEA: 9.1 ± 2.2, 6.4 ± 2.3, 5.5 ± 2.8, and 5.1 ± 2.0 IU/ml (P &lt; 0.01 vs. baseline, by ANOVA); placebo: 9.0 ± 2.1, 10.4 ± 2.2, 9.5 ± 2.2, and 9.6 ± 2.1 IU/ml (P &lt; 0.01, by ANOVA)]. DHEA supplementation also decreased steady state plasma glucose [DHEA: baseline, 178.9 ± 12.2; 12 wk, 132.0 ± 12.8 mg/dl (P &lt; 0.01, by ANOVA); placebo: 181.0 ± 13.8 and 179.6 ± 12.4 mg/dl (P &lt; 0.01, by ANOVA)]. In contrast, steady state plasma insulin did not change during the study in either group. The low dose DHEA supplementation improves vascular endothelial function and insulin sensitivity and decreases the plasminogen activator inhibitor type 1 concentration. These beneficial changes have the potential to attenuate the development of age-related disorders such as cardiovascular disease.

scholarly journals Hemostatic Risk Factors and Insulin Sensitivity, Regional Body Fat Distribution, and the Metabolic Syndrome

2005 ◽  
Vol 90 (1) ◽  
pp. 190-197 ◽  
Author(s):  
I. F. Godsland ◽  
D. Crook ◽  
A. J. Proudler ◽  
J. C. Stevenson
Keyword(s):  
Metabolic Syndrome ◽  
Factor Analysis ◽  
Insulin Sensitivity ◽  
Plasminogen Activator ◽  
Body Fat ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
The Metabolic Syndrome ◽  
Regional Adiposity ◽  
Activator Inhibitor

Abstract Disturbances in the thrombotic and fibrinolytic systems are a feature of insulin resistance, obesity, and the metabolic syndrome. However, there are few studies in which these relationships have been explored in mainly asymptomatic individuals using sophisticated measures of insulin sensitivity and regional adiposity. Variables of the hemostatic system were measured in 106 men (aged 32–68 yr; body mass index, 20–34 kg/m2). Insulin sensitivity was measured by minimal model analysis and regional adiposity by dual energy x-ray absorptiometry. Clustering of intercorrelated variables was assessed by the statistical technique of factor analysis. Plasma levels of procoagulant factors VII and X, anticoagulant proteins C and S, and plasminogen activator inhibitor-1 correlated positively with total and percent central body fat (r = 0.25–0.38; P &lt; 0.05) and negatively with insulin sensitivity (except protein S; r = −0.24 to −0.35; P &lt; 0.05). On factor analysis, procoagulant factors VII and X, proteins C and S, and plasminogen activator inhibitor-1 were components of the cluster of variables that explained the greatest proportion of the variance in the data (39.2%). Other variables included in this cluster were those typical of the metabolic syndrome and also serum γ-glutamyl transferase activity. These results suggest that factors VII and X and proteins C and S are features of the intercorrelated disturbances of the metabolic syndrome. Associations with adiposity and liver enzyme activity suggest the involvement of hepatic fat deposition.

scholarly journals Principal Component Analysis of Adipocytokines and Insulin Associate with Risk Factors of Cardiovascular Diseases

2020 ◽  
Author(s):  
Habib yarizadeh ◽  
Leila Setayesh ◽  
Moein Askarpour ◽  
Sara Pooyan ◽  
Seyedeh Forough Sajjadi ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Density Lipoprotein ◽  
Plasminogen Activator Inhibitor ◽  
Interleukin 1 Beta ◽  
C Reactive Protein ◽  
Plasminogen Activator Inhibitor 1 ◽  
Monocyte Chemoattractant ◽  
Reactive Protein ◽  
Galectin 3 ◽  
Activator Inhibitor

Abstract Objectives : Obesity plays an important role in the development of chronic diseases like cardiovascular diseases and diabetes. The possible underlying mechanism for this connection is that adipose tissue secretes an array of chemical messenger adipokines proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). This study aimed to investigate the linkage between adipocytokines and insulin with the cardiovascular disease risk, with particular reference to the adipokines galectin-3, plasminogen activator inhibitor-1, interleukin-1-beta, C-reactive protein, and monocyte chemoattractant protein. Result: Two patterns were identified. The first pattern was galectin-3, plasminogen activator inhibitor-1 and interleukin-1-beta and the second one was C-reactive protein, insulin and monocyte chemoattractant protein-1. The second pattern was strongly associated with the higher scores for resting metabolic rate, diastolic blood pressure, homeostasis model insulin resistance index, lipid profile (except low density lipoprotein, total cholesterol), and body composition parameters (except fat free mass index and waist hip ratio), while negatively associated with age and high density lipoprotein level (all p < 0.05). The first pattern was, however, significantly associated with body fat mass, obesity degree percentage, waist circumference, fat mass index, and waist hip ratio (P < 0.05 for all).

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